The Value of Donor Lymphocyte Infusions In Unstable Mixed Chimerism In Patients with Beta Thalassemia.

Abstract 4521

The only curative option for ß talasemia remains allogeneic hematopoietic stem cell transplantation (HSCT) to correct the genetic defect and provide a normal hemoglobin level in the recipient. Engraftment of donor derived cells is necessary for a success of transplantation. However, it has been shown that complete donor hematopoesis is not essential for sustained engraftment in thalassemia. Donor and recipient cells may coexist and produce a functional graft commonly referred to as donor/recipient mixed chimerism (MC) even with a low amount of engrafted donor cells. We documented our experience in a cohort of 19 beta thalassemia patients receiving DLI (donor lymphocyte infusions) following 21 transplantations with unstable mixed chimerism (MC). Seven patients received DLI with the indication of having more than 25% residual host cells (RHC) (MClevel3(residual host cells>25%)) early after transplantation and assigned as early-DLI group. Four patients although had MClevel3 in the early period, received deferred DLI and assigned as late-DLI group. The difference between these two groups, in respect to preserving functional graft, was not found statistically significant. However the chimerism kinetics of these early and late-DLI groups were also different and a slower decline in percentage of donor cells were observed in patients preserving grafts. Ten patients received DLI in the later period and although a significant increase in percentage of donor cells was not detected, increase in hemoglobin levels was provided. The infusions were safe with acceptable risk for GVHD. We believe that patients with more than 25% of RHC within two months early intervention with DLI seems feasible. Deferring DLI to a later period especially if the decrease in percentage of donor cells is so prompt, seems less effective. In the later period, we propose to consider the hemoglobin level as the main determinative factor for DLI application rather than the percentage of donor cells in line with expectance of better long-term tolerance. A better understanding of the mechanisms underlying the occurrence of persistent MC and strategies for induction and maintenance of tolerance will provide better interventions and outcomes for these patients.